S-Alkylation of a thioamide via SN2 reaction
SyntheticPage 89
DOI:
Submitted: August 16, 2001, published: August 17, 2001
Authors
Stephen Caddick (s.caddick@sussex.ac.uk)
A contribution from
Chemicals
Substrate(1.05 mmoles),
Methyl iodide (16 mmoles),
Ether (8 ml).
Methyl iodide (16 mmoles),
Ether (8 ml).
Procedure
Methyl iodide (1 ml, 16 mmoles) added to the substrate (200 mg, 1.05 mmoles) in ether (8ml) and stirred at room temperature overnight. Solvent removed to give the title compound as a white solid. Yield 260 mg, 78%.
Author Comments
If the reaction mixture is sufficiently concentrated then the (white solid) product can precipitate from the ether solution. If dichloromethane is used then the salt is usually soluble (this can be useful for the preparation of thioimino ethers). Note heating these reaction can lead to reversion presumably as iodide can demethylate. If applying this reaction to long chain alkyl halides then washing of the crude product with cold solvent (ether/petrol) might be required to remove excess electrophile.
Data
7.4, 5H, s, Ph; 4.9, 2H, s, CH2Ph; 4.15, 2H, t, CH2N; 3.8, 2H, t, CH2CSMe; 3.0, 3H, s, SMe; 2.4, 2H, m, CH2
Lead Reference
For generation of thiomidate salts and utility in natural product synthesis see: C. H. Heathcock, S. Davidsen, S. Mills, M. A. Sanner, J. Am. Chem. Soc. 1986, 108, 5650